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Bench Science |
Department of Nephrology,1 University of Heidelberg; Department of Pathology,2 University of Heidelberg, Heidelberg, Germany; and Gambro Corporate Research,3 Lund, Sweden and Hechingen, Germany
Correspondence to: V. Schwenger, Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120 Heidelberg, Germany. vedat.schwenger{at}med.uni-heidelberg.de
Background: It has been shown that glucose degradation
products (GDP) generated during heat sterilization of peritoneal dialysis (PD)
fluids impair the peritoneal membrane locally, then enter the systemic
circulation and cause damage to the remnant kidney. Here we examined in
subtotally nephrectomized (SNX) rats whether GDP also affect the
cardiovascular system. Materials and Methods: Standard 5/6 nephrectomy was
carried out in Sprague–Dawley rats; other rats were sham operated and
left untreated for 3 weeks. Through an osmotic mini-pump, SNX+GDP group
received GDP intravenously for 4 weeks; the SNX and the sham-operated groups
remained without GDP. The experiment was terminated for all groups 7 weeks
postoperatively. We analyzed cardiovascular damage by serum analyses and
immunohistochemical investigation. Results: In SNX+GDP animals, expression of the advanced
glycation end product (AGE) marker carboxymethyllysine and receptor of AGE
(RAGE) were significantly higher in the myocardium and the aorta compared to
the SNX rats. We also found significantly higher levels of apoptosis measured
by caspase 3 staining in the cardiovascular system in the SNX+GDP group.
Moreover, we observed a more pronounced expression of oxidative stress in the
SNX+GDP rats compared to the SNX rats. In serum analyses, advanced oxidation
protein products and reactive oxygen species were increased, as was
immunohistochemical endothelial nitric oxide synthase. Conclusions: In addition to local toxic effects, GDP
cause systemic toxicity. Here we showed that, in SNX rats, administration of
GDP increased cardiovascular damage. In particular, we found increased levels
of AGE, RAGE, oxidative stress, and apoptosis. Whether these findings are of
clinical relevance has to be further investigated.
KEY WORDS: Glucose degradation products; cardiovascular damage; advanced glycation end products; systemic toxicity; oxidative stress.
Received 12 February 2009; accepted 23 March 2009.
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